Research in the Laboratory of Dr. Peter Crawford
Obesity and cardiovascular disease are among the leading causes of morbidity and mortality worldwide. Our research focuses on the interplay between intermediary metabolism and these disease processes. Derangements in the processing of carbohydrates, fats, and amino acids are central drivers of disease pathogenesis, but the roles of another metabolic fuel class, ketone bodies, are less well understood. We use novel genetic mouse models with engineered deficiencies in ketone body metabolism to study the metabolic shifts that occur in response to obesity, cardiovascular disease, and dynamic environmental challenges. From these models, we have developed new perspectives of how metabolism adapts in obesity, diabetes, nonalcoholic fatty liver disease (NAFLD/NASH), and cardiomyopathy; how these adaptations ultimately prove deleterious, and how innovative and personalized nutritional and pharmacological therapies may mitigate these adverse responses.
We leverage recent advances in stable isotope tracer based NMR and mass spectrometry-based untargeted metabolomics technologies to study metabolism on a systems level, and we also employ established techniques in molecular cell biology and biochemistry to reveal phenotypic shifts at the cellular level. Complex in vivo phenotyping methodologies is strategically aligned with these sophisticated chemical profiling platforms to generate high-resolution phenotypic pictures. In addition to our mouse studies, we perform studies in humans to learn how alterations of ketone metabolism and related pathways may serve as diagnostic biomarkers and therapeutic targets for obesity, diabetes, NAFLD/NASH, heart failure/CHF, and metabolic maladaptations that can occur in any disease state.